A high incidence of Shigella-induced arthritis in a primate species: majorhistocompatibility complex class I molecules associated with resistance and susceptiblity and their relationship to HLA-B27

The human major histocompatibility complex (MHC) class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spon dyloarthropathies. Rodents that express HLA-B27 develop spondyloarthropathi es. implicating HLA-B27 in the etiology of these disorders, To determine wh ether an HLA-B27-like molecule was associated with spondyloarthropathies in nonhuman primates, we analyzed the MHC class I cDNAs expressed in a cohort of rhesus macaques that developed reactive arthritis after an outbreak of shigellosis. We identified several cDNAs with only limited sequence similar ity to HLA-B27, Interestingly, one of these MH molecules had a B pocket ide ntical to that of HLA-B39. Pool sequencing of radiolabeled peptides bound b y this molecule demonstrated that, like HLA-B27 and HLA-B39, it could bind peptides with arginine at the second position. However, extensive analysis of the MHC class I molecules in this cohort revealed no statistically signi ficant association between any particular MHC class I allele and susceptibi lity to reactive arthritis. Furthermore, none of the rhesus MHC class I mol ecules bore a strong resemblance to HLA-B27, indicating that reactive arthr itis can develop in this animal model in the absence of an HLA-B27-like mol ecule. Surprisingly, there was a statistically significant association betw een the rhesus macaque MHC A locus allele, Mamu-A*12. and the absence of re active arthritis following Shigella infection.